B-cell activation in human plasma cell dyscrasias.

Abstract

We studied the abnormal in vitro polyclonal B-cell activity observed in patients with multiple myeloma and Waldenström's macroglobulinaemia. Numbers of cells spontaneously secreting immunoglobulin (Ig) in freshly isolated suspensions of peripheral blood mononuclear cells and pokeweed mitogen (PWM) stimulated cultures of blood mononuclear cells were determined with a protein A reverse haemolytic plaque assay. These data were correlated with both the clinical and laboratory parameters of disease. Furthermore, Ig secreted into supernatants of PWM-stimulated cultures was examined by a light chain radioimmunoassay for evidence of in vitro activation of malignant B-cells. The mean level of circulating immunoglobulin secreting cells (IgSC) in patients was elevated when compared to that of normal subjects. The highest values were observed in those patients with the highest levels of serum paraprotein. However, experiments with cycloheximide suggested that such increased circulating IgSC values were often caused by the detection of Ig passively adsorbed to blood mononuclear cells. The studies with PWM stimulation of blood mononuclear cells were particularly revealing. Cultures of patient blood mononuclear cells with PWM showed depressed IgSC responses as a group compared to cultures of normal blood mononuclear cells; nevertheless, approximately half the patients demonstrated a sizeable response to PWM. No evidence for preferential activation of Ig secretion by the malignant B-cell clone was observed. Impaired PWM induced responses were associated with advanced or progressive clinical disease.